Malignant mesothelioma is a tumor which is extremely recalcitrant to treatment by chemotherapeutic agents. It was of interest to test mesothelioma cell lines for expression of the multiple drug resistance (MDR) gene. If this gene were expressed at a high level in the mesothelioma cells, its action might be expected to be at the basis of the resistance of this tumor type to chemotherapy. RNA was prepared and tested from 16 human mesothelioma cell lines, 2 normal human mesothelial cells, and 3 normal human mesothelial cells immortalized by the SV40 T antigen. Of all samples tested only 2 were positive for expression of the MDR gene. We conclude that the MDR gene product is not the protein of importance for the resistance to chemotherapeutic agents shown by human mesothelioma. Therefore, strategies which would specifically inactivate or reverse the action of this gene product are not relevant to the mesothelioma therapeutic dilemma.